Burden of serious fungal infections in Dominican Republic Harish Gugnani*, David W Denning1,2 and Carlos Rodriguez-Taveras** *Professor of Microbiology & Epidemiology, St. James School of Medicine, Kralendjik, Bonaire (Dutch Caribbean), UHSM email: harish.gugnani@gmail **Head, Division of Infectious Diseases, Hospital Central de las Fuerzas Armadas Santo University Hospital Domingo, Dominican Republic, email: [email protected] of South Manchester NHS Foundation Trust 1The University of Manchester, Manchester Academic Health Science Centre, Manchester, U.K. LEADING 2 INTERNATIONAL The University Hospital of South Manchester, National Centre (NAC) Manchester, U.K. in association FUNGAL with the LIFE program at www.LIFE-worldwide.org EDUCATION

Background and Rationale Information on the incidence and prevalence of fungal infections in Dominican Republic (DR) is very scanty. Pityriasis versicolor and caused by audouinii and tonsurans are common in children (Arenas et al. 2001, 2010). There is report of one case of disseminated (Caplivski et al. 2005). A case of meningitis successfully treated with has also MR image of an been reported (Mikolichet al. 1996). We estimated the burden of fungal immunocompetent 25-yr- infections in Dominican Republic from published literature and old female from DR with Aspergillus meningitis modelling. [Mikolichet al. Clin. Infect. Dis 1996;23:1318-9.]

Table 1. Estimated burden of fungal disease in Dominican Republic Methods None HIV Respiratory Cancer ICU Total n/ There were no reports on fungal infection rates hfrom DR; so every /AIDS /Tx 100k estimate is based on modelling. We extracted data from the WHO STOP Oesophageal ? 3,805 - ? - 3,805 36.7 TB program and UNAIDS annual reports. We used specific populations at risk and fungal infection frequencies in those populations to estimate Candidaemia - - - 353 151 136 5 national incidence or prevalence. Allergic bronchopulmonary Candida - - - - 76 76 0.75 peritonitis aspergillosis (ABPA) and serious asthma with fungal sensitization (SAFS) estimates were based on a 9.97% adult clinical asthma rate (To et al, RVVC (4x/year+) 158,134 - - - - 158,134 3,134 BMC Pub Health 2012) and chronic pulmonary aspergillosis (CPA) on TB ABPA - - 25,149 - - 25,149 249 rates. Other assumptions were based on incidence rates reported in the SAFS - - 33,197 - - 33,197 329 local and international literature. The denominator included the overall CPA - - 1,374 - - 1,374 52 DR population, number of patients with HIV/AIDS and respiratory diseases. IA - - - 61 ? ? 0.8 - - - 20 - ? 0.2 CM ? 240 - - - 240 2.4 Results PCP - 1,920 ? ? - 1,920 19 Histoplasmosis ? ? ? - - ? ? The DR population was estimated to be 10,090,000 million people Fungal keratitis ? - - - - - ? (2009), of whom 31% are children (0-14 years) and 9% are >60 years Tinea capitis ? - - - - ? ? old. The adult asthma population was estimated at 1 million. Using a Total burden 158,134+ 5,101+ 59,720 434+ 227+ 229,681+ 2.5% rate of ABPA based on other studies (Denning et al, 2013), DR is estimated estimated to have 25,150 ABPA and 34,000 SAFS cases (250 and ABPA=Allergic bronchopulmonary aspergillosis, CM=Cryptococcal meningitis, PCP= pneumonia, 529/100,000 respectively). Further, 3,300 cases of pulmonary TB were IA=Invasive aspergillosis, CPA=Chronic pulmonary aspergillosis, RVVC=Recurrent vulvovaginal candidiasis, SAFS=Severe asthma with fungal sensitisation reported in 2011, which is estimated to lead to 145 new CPA cases annually and a 5 year prevalence of 458, assuming a 15% death annual death rate. If TB accounts for 33% of the cases then the total CPA prevalence is 1,374 cases in DR. Invasive aspergillosis in haematological Conclusion malignancy is estimated to affect 61 patients, assuming a 10% attack We estimated that over 220,000 people in DR probably suffer from rate. If the incidence of candidaemia is 5/100,000, 505 cases of serious fungal infections each year, most related to asthma, prior TB, candidaemia and 76 cases of Candida peritonitis post-surgery occur recurrent vulvovaginal candidiasis (RVVC), and HIV infection. Local annually. An estimated 158,134 women have >4 attacks of vaginal epidemiological studies are urgently required to establish the validity of candidiasis annually (6% women >15 yrs). The burden of HIV/AIDS is these estimates. estimated to be 62,000+ patients, 1.1% of adults, of whom 24,000 have CD4 counts <350/uL and are not being treated. Assuming 50% of these patients have CD4 cell counts <200/uL then 90% probably develop oral References candidiasis, (5,400 patients) and for oesophageal candidiasis 20% or 1. Arenas R, Torres E, Amaya M et al. (2010) Emergence of Microsporumaudouinii and as causative organisms of tinea capitis in the Dominican Actas Dermosifiliogr 101:330-5. 3,800 cases are estimated annually. Assuming 10% of those not on 2. Arenas R, Isa-Isa R, Cruz AC. (2001) Pityriasis versicolor in Santo Domingo, Dominican Republic. In vivo ARVs progress to a life-threatening opportunistic infections each year, morphological data of Malasezzia spp. in 100 cases. Rev Iberoam Micol. 18: 29-32 and that the rate of (PCP) is 80% and 3. Caplivski D, Salama C; Huprikar S; Bottone, EJ. (2005) Disseminated histoplasmosis in five immunosuppressed patients: clinical, diagnostic, and therapeutic perspectives. Rev Med. Microbiol 16: cryptococcal meningitis (CM) 10%, 1,920 PCP cases and 240 CM cases 1-7 are anticipated annually. It wasn't possible to estimate the burden of 4. Denning DW, Pleuvry A, Cole DC. (2013) Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults. Med Mycol 51: 361-370. histoplasmosis, or fungal keratitis, and some estimates are incomplete, 5. Mikolich DJ, Kinsella LJ, Skowron G, Freidman J, Sugar AM. Aspergillus meningitis in an immuno- notably invasive aspergillosis, as relevant data are not available. competent adult successfully treated with itraconazole. Clin Infect Dis 1996; 23:1318-1319.